Researchers at the University of Chicago are engaged in a wide range of radiation related cancer research. The objective of this application is to provide a modern, high precision image guided experimental X-ray irradiation facility for animals and cells to support this research and to enable new research initiatives. Currently available facilities are a 30 year old orthovoltage X-ray unit, plus gamma-ray irradiators which are incapable of anything other than whole-body irradiation. Modern radiotherapy for patients achieves precision on the order of a few millimeters. Anatomical regions adjacent to the treatment target can be largely spared from radiation injury. A highly conformal radiation dose distribution can be used to ablate a metastatic lesion, or in a radiation inducible gene therapy approach which spatially confines the gene therapy effect. Research on the radiation responses underlying these therapies, and other radiation related biomedical investigation, is conducted by our researchers, but the irradiation facilities available pose severe limitations to the sophistication of the radiation protocols that can be used. The device requested is a Precision X-ray X-RAD225Cx Image Guided Biological Irradiator System, integrating an imaging device and the X-ray source on a rotating gantry, analogous to current clinical radiation therapy machines. Low dose images in radiographic or cone-beam CT scanning mode show the position of the animal before the experimental dose. Just as in patient treatment, this enables setting up the animal so that the collimated beam irradiates the desired region of anatomy and not elsewhere. The imaging capabilities of the system also facilitate its use in investigation of innovations in CT scanning. Major users of this facility have currently funded research in (1) development and validation of chemopreventive strategies to reduce risk of therapy-related hematologic malignancies in radiation and/or chemotherapy patients, using a lung micrometastasis model. (D.R. Grdina);(2) Investigation of mechanisms of resistance to radio-inducible gene therapy, where conformal radiation is used to turn on therapeutic gene expression locally in mouse models of cancer (R.R. Weichselbaum);(3) identification of an image-based "signature" of the effects of radiation-induced gene therapy in a head and neck cancer model, a potential biomarker for early assessment of treatment response (R.R. Weichselbaum);(4) investigation of a radiation inducible HSV-1 oncolytic therapy for brain tumors in intracerebral and flank mouse models (R.R. Weichselbaum, P01 of R. Whitley, University of Alabama-Birmingham);(5) investigation of innovative methods of CT scan acquisition and reconstruction (X. Pan). Additional research using the facility will initially include: (1) application of a novel EPR oxygen imaging modality in radiation biology (H.J. Halpern);(2) investigation of mechanisms of radiation-induced lung injury (Joe G.N. Garcia);(3) investigation of the role of NFkB in therapy of gliomas (B. Yamini).